Sarah Bos

90 CHAPTER 6 Procoagulant strategies that are commonly used include fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), and less often recombinant factor VIIa (rFVIIa). Fresh frozen plasma is frequently used during partial hepatectomy and OLT to treat perceived coagulopathy or prevent bleeding. The disadvantage of the use of FFPs is that often large volumes are needed to achieve meaningful increases in factor levels. Moreover, the efficacy of FFP as a procoagulant agent continues to be debated both in the general population(23,24), and in patients with liver disease(25,26). The advantage of PCCs over FFP is the low volume and the potential to fully normalize factor levels, while the disadvantage is that PCCs do not contain all procoagulant factors. A strategy combining PCC with fibrinogen concentrate has been used as first line hemostatic management during OLT(27). Heparins are frequently used in anticoagulant management of patients undergoing HPB surgery. Importantly, monitoring of heparins in these patients who have decreased antithrombin levels is complicated by the underestimation of heparin levels when tested by an anti-Xa assays(28). Although direct oral anticoagulants (DOACs) are not indicated in surgical settings beyond major hip or knee surgery, there are theoretical advantages of DOACs in the HPB surgical setting, as antithrombin levels can become very low in the early postoperative period, particularly following OLT and major partial hepatectomies(14,19). Of note, although the clinical use of DOACs in patients with liver disease in increasing(29), DOACs have never been studied in clinical trials in this patient population. In addition, in package inserts, DOACs are contraindicated or advised to use cautiously in patients with advanced liver disease. We have recently demonstrated that the in vitro efficacy of pro- and anti-hemostatic drugs is profoundly different in patients with compensated cirrhosis and in those who have cirrhosis and are critically ill(30,31). This likely relates to differences in the profound alterations in their hemostatic systems. In this study we aimed to assess the efficacy of both pro- and anticoagulant drugs in plasma of patients undergoing HPB surgery, as hemostatic changes in these patients are also frequently substantial. Better understanding of the efficacy of commonly used pro- and anticoagulant approaches may inform future clinical studies on optimizing use of pro- and anticoagulants in this patient population. Methods Patients and setting The study was performed at King’s College Hospital, a 950-bed tertiary hospital in London, United Kingdom, from September 2017 until December 2017. Sixty